A new direct labeling technique for proteins with technetium-99m (99mTc) has been developed and makes use of borohydride and stannous chloride. The method is simple and reproducible and gives a high labeling efficiency and high retention of biological activity for proteins, including polyclonal immunoglobulin (Ig), antifibrin monoclonal antibody, tissue type plasminogen activator, fibrinogen and low density lipoprotein (LDL). This method can be used in kit-format and takes about 20 min preparation time at room temperature. Both in vitro and in vivo studies indicate good stability of the label. In vivo, mice and rabbit images show significant accumulation of 99mTc-Ig at an inflammation area, 99mTc-antifibrin at a thrombus site and 99mTc-LDL in atherosclerotic lesions. The method is attractive for routine research and clinical purposes.